Drug-induced QT prolongation when QT interval is measured in each of the 12 ECG leads in men and women in a thorough QT study.

Lead II is commonly used to study drug-induced QT prolongation. Whether other ECG leads too show comparable QT prolongation is not known. We studied moxifloxacin-induced QT prolongation in a thorough QT study in healthy subjects (54 males, 43 females). Placebo-subtracted change from baseline in QTc corrected by Fridericia's method (ΔΔQTcF) at 1, 1.5, 2 and 4 hours after moxifloxacin was studied in all 12 leads. Unacceptably wide 90% confidence interval (CI) for ΔΔQTcF was seen in three leads; these leads also had maximum ECGs with flat T waves (60% in aVL, 45% in lead III and 42% in V1). After excluding ECGs with flat T waves, 90% lower CI of ΔΔQTcF was ≥ 5 ms in all leads except leads III, aVL and V1 in men. The 90% lower CI exceeded 5 ms in these leads in women despite wide 90% CIs because of greater mean ΔΔQTcF. Leads III, aVL and V1 should be avoided when measuring QT interval in thorough QT studies.

Choice of an alternative lead for QT interval measurement in serial ECGs when Lead II is not suitable for analysis.

INTRODUCTION: Conventionally, QT interval is measured in lead II. There are no data to select an alternative lead for QT measurement when it cannot be measured in Lead II for any reason. METHODS AND RESULTS: We retrospectively analyzed ECGs from 1906 healthy volunteers from 41 phase I studies. QT interval was measured on the median beat in all 12 leads. The mean difference in QT interval between lead aVR and in Lead II was the least, followed by aVF, V5, V6 and V4; lead aVL had maximum difference. The T wave was flat (<0.1 mV) in Lead II in 6.9% of ECGs; it was also flat in 20% of these ECGs (1.4% of all ECGs) in Leads aVR, aVF and V5. CONCLUSIONS: When QT interval cannot be measured in Lead II, the best alternative leads are aVR, aVF, V5, V6 and V4 in that sequence. It differs maximally from that in Lead II in Lead aVL.

Early repolarization and short QT interval in healthy subjects.

BACKGROUND: An early repolarization (ER) pattern is common in ECGs from patients with ventricular fibrillation (VF). These patients with ER have shorter QT intervals. Morphological variants of the ER pattern also have been associated with idiopathic VF, but their prevalence in healthy subjects is unclear. OBJECTIVE: The purpose of this study was to study the prevalence of ER and its morphological variants, and its association with the QTc interval in healthy subjects. METHODS: Digital ECGs from 1886 healthy subjects from Phase I clinical trials were analyzed by a central ECG laboratory. RESULTS: ER, defined as J-point elevation ≥0.1 mV in ≥2 contiguous leads, was present in 514 subjects (27.3%), of whom 505 (98.2%) were males. The prevalence of ER declined progressively with increasing age. ER pattern was seen in lateral leads (I, aVL, V(4)-V(6)) in 26.1%, in inferior (II, III, aVF) or inferolateral leads in 8%, and was global in 1.9%. The terminal portion of the QRS complex was notched in 43.1% and slurred in 56.9%. Notching was common in inferior/lateral leads, and slurring was common in anterior leads. A non-ascending ST segment was seen in 71% of ECGs with a notched pattern but in only 12.3% of ECGs with a slurred pattern. The ER group had slower heart rates (9.3 ± 13.3 bpm [mean difference ± SD], P <.001) and shorter QTc intervals (QTcB = 20.2 ± 25.6 ms, QTcF = 11.0 ± 21.9 ms; P <.001). Four subjects in each group had a short QT interval (QTcF <350 ms). CONCLUSION: ER and all of its variants are common in healthy young males with slower heart rates and slightly shorter QTc intervals. A short QT interval (QTcF <350 ms) is rare.

Safe substitution to zidovudine among HIV-infected patients initiated on stavudine-containing highly active antiretroviral therapy from a resource-limited setting.

OBJECTIVE: To describe the safe substitution with zidovudine (AZT) among South Indian HIV-infected patients who were initiated with stavudine (d4T)-containing highly active antiretroviral therapy (HAART) due to anemia. METHODS: Therapy-naïve patients initiating HAART between January 2006 and December 2007 and who had had d4T substituted for AZT at a tertiary HIV referral center in India were analyzed. RESULTS: Six hundred and nineteen patients initiated d4T-containing HAART (median CD4 110 cells/microl; median hemoglobin 10.4 g/dl) during the study period. Subsequently half of these patients substituted d4T for AZT (median CD4 350 cells/microl; median hemoglobin 12.8 g/dl). After substituting with AZT, three patients (2.7%) who substituted after less than 6 months and one patient (0.6%) who substituted at between 6 and 12 months developed anemia. Patients who substituted after less than 6 months had significantly higher median CD4 cell counts at 1-month and 6-months of follow-up than patients who substituted at between 6 and 12 months (p<0.05). Few patients (1.6%) experienced treatment failure; about a tenth of patients developed d4T-related toxicities. CONCLUSION: Few patients developed anemia (1.4%) within 6 months of substitution with AZT. In settings where tenofovir is either expensive or not available and where patients are anemic, initiating d4T followed by prompt substitution with AZT can be a safe and tolerable treatment option.